This project involves a multidisciplinary approach to the investigation of the pathogenesis of several forms of adrenal-related hypertension in experimental animals. The role of 11-deoxycorticosterone and other mineralocorticoids in adrenal-regeneration and androgen-induced hypertension will be evaluated. Determination of such mineralocorticoids in the blood of hypertensive animals will be correlated with adrenal cortical structure and function. In the case of the androgen-model of experimental hypertension, studies will be carried out to elucidate the metabolism of androgens within the adrenal cortex of the rat with a view to explaining the molecular events associated with the inhibition of steroid hydroxylase systems leading to excess secretion of hypertensinogenic steroids. The interaction of androgens with the cytochrome P450 systems of the adrenal cortex will be evaluated by radioautography. Rats of the Wistar/Furth strain have been identified as having resistance to the development of mineralocorticoid/salt hypertension. Experiments are designed to explain this resistance and will involve assessment of mineralocorticoid receptors in the kindey, metabolism of corticosteroids in sensitive and resistant strains and interaction of mineralocorticoids with receptors in the brain. Attempts will be made to develop a mineralocorticoid/salt related hypertension in cortisol secretors such as the hamster and Mongolian gerbil. Other factors controlling the inner zone of the adrenal cortex will be examined in forms of experimental hypertension which are adrenal-related such as adrenal-regeneration hypertension. Activity of any such factors will be compared in strains of rat which are sensitive and resistant to mineralocorticoid hypertension.